Does Qualification Drive Innovation? A Microeconometric Analysis Using Linked-employer-employee Data

Degree-level science and engineering skills as well as management and leadership skills are often referred to as a source of innovative activities within companies. Broken down by sectoral innovation patterns, this article examines the role of formal education and actual occupation for product innovation performance in manufacturing firms within a probit model. It uses unique micro data for Germany (LIAB) that contain detailed information about innovative activities and the qualification of employees. We find significant differences of the human capital endowment between sectors differentiated according to the Pavitt classification. Sectors with a high share of highly skilled employees engage in product innovation above average (specialized suppliers and science based industries). According to our hitherto estimation results, within these sectors the share of highly skilled employees does not, however, substantially increase the probability to be an innovative firm.innovation, human capital, qualification, sectoral innovation system

Improved resource efficiency and cascading utilisation of renewable materials

In light of various environmental problems and challenges concerning resource allocation, the utilisation of renewable resources is increasingly important for the efficient use of raw materials. Therefore, cascading utilisation (i.e., the multiple material utilisations of renewable resources prior to their conversion into energy) and approaches that aim to further increase resource efficiency (e.g., the utilisation of by-products) can be considered guiding principles. This paper therefore introduces the Special Volume “Improved Resource Efficiency and Cascading Utilisation of Renewable Materials”. Because both research aspects, resource efficiency and cascading utilisation, belong to several disciplines, the Special Volume adopts an interdisciplinary perspective and presents 16 articles, which can be divided into four subjects: Innovative Materials based on Renewable Resources and their Impact on Sustainability and Resource Efficiency, Quantitative Models for the Integrated Optimisation of Production and Distribution in Networks for Renewable Resources, Information Technology-based Collaboration in Value Generating Networks for Renewable Resources, and Consumer Behaviour towards Eco-friendly Products. The interdisciplinary perspective allows a comprehensive overview of current research on resource efficiency, which is supplemented with 15 book reviews showing the extent to which textbooks of selected disciplines already refer to resource efficiency. This introductory article highlights the relevance of the four subjects, presents summaries of all papers, and discusses future research directions. The overall contribution of the Special Volume is that it bridges the resource efficiency research of selected disciplines and that it presents several approaches for more environmentally sound production and consumption

Rapid eradication of colon carcinoma by Clostridium perfringens Enterotoxin suicidal gene therapy

Background Bacterial toxins have evolved to an effective therapeutic option for cancer therapy. The Clostridium perfringens enterotoxin (CPE) is a pore- forming toxin with selective cytotoxicity. The transmembrane tight junction proteins claudin-3 and -4 are known high affinity CPE receptors. Their expression is highly upregulated in human cancers, including breast, ovarian and colon carcinoma. CPE binding to claudins triggers membrane pore complex formation, which leads to rapid cell death. Previous studies demonstrated the anti-tumoral effect of treatment with recombinant CPE-protein. Our approach aimed at evaluation of a selective and targeted cancer gene therapy of claudin-3- and/or claudin-4- expressing colon carcinoma in vitro and in vivo by using translation optimized CPE expressing vector. Methods In this study the recombinant CPE and a translation optimized CPE expressing vector (optCPE) was used for targeted gene therapy of claudin-3 and/or -4 overexpressing colon cancer cell lines. All experiments were performed in the human SW480, SW620, HCT116, CaCo-2 and HT-29 colon cancer and the isogenic Sk-Mel5 and Sk-Mel5 Cldn-3-YFP melanoma cell lines. Claudin expression analysis was done at protein and mRNA level, which was confirmed by immunohistochemistry. The CPE induced cytotoxicity was analyzed by the MTT cytotoxicity assay. In addition patient derived colon carcinoma xenografts (PDX) were characterized and used for the intratumoral in vivo gene transfer of the optCPE expressing vector in PDX bearing nude mice. Results Claudin-3 and -4 overexpressing colon carcinoma lines showed high sensitivity towards both recCPE application and optCPE gene transfer. The positive correlation between CPE cytotoxicity and level of claudin expression was demonstrated. Transfection of optCPE led to targeted, rapid cytotoxic effects such as membrane disruption and necrosis in claudin overexpressing cells. The intratumoral optCPE in vivo gene transfer led to tumor growth inhibition in colon carcinoma PDX bearing mice in association with massive necrosis due to the intratumoral optCPE expression. Conclusions This novel approach demonstrates that optCPE gene transfer represents a promising and efficient therapeutic option for a targeted suicide gene therapy of claudin-3 and/or claudin-4 overexpressing colon carcinomas, leading to rapid and effective tumor cell killing in vitro and in vivo

Seismic interpretation and structural restoration of the Heligoland glaciotectonic thrust-fault complex: Implications for multiple deformation during (pre-)Elsterian to Warthian ice advances into the southern North Sea Basin

Despite a long history of research, the locations of former ice-margins in the North Sea Basin are still uncertain. In this study, we present new palaeogeographic reconstructions of (pre-) Elsterian and Warthian ice-margins in the southeastern North Sea Basin, which were previously unknown. The reconstructions are based on the integration of palaeo-ice flow data derived from glaciotectonic thrusts, tunnel valleys and mega-scale glacial lineations. We focus on a huge glaciotectonic thrust complex located about 10 km north of Heligoland and 50 km west of the North Frisian coast of Schleswig-Holstein (Northern Germany). Multi-channel high-resolution 2D seismic reflection data show a thrust-fault complex in the upper 300 ms TWT (ca. 240 m) of seismic data. This thrust-fault complex consists of mainly Neogene delta sediments, covers an area of 350 km2, and forms part of a large belt of glaciotectonic complexes that stretches from offshore Denmark via northern Germany to Poland. The deformation front of the Heligoland glaciotectonic complex trends approximately NNE-SSW. The total length of the glaciotectonic thrust complex is approximately 15 km. The thrust faults share a common detachment surface, located at a depth of 250–300 ms (TWT) (200–240 m) below sea level. The detachment surface most probably formed at a pronounced rheological boundary between Upper Miocene fine-grained pro-delta deposits and coarser-grained delta-front deposits, although we cannot rule out that deep permafrost in the glacier foreland played a role for the location of this detachment surface. Restored cross-sections reveal the shortening of the complex along the detachment to have been on average 23% (ranging from ca. 16%–50%). The determined ice movement direction from east-southeast to southeast suggests deformation by an ice advance from the Baltic region. The chronospatial relationship of the thrust-fault complex and adjacent northwest-southeast to northeast-southwest trending Elsterian tunnel valleys implies a pre-Elsterian (MIS 16?) age of the glaciotectonic complex. However, the age of these Elsterian tunnel valleys is poorly constrained and the glaciotectonic complex of Heligoland may also have been formed during an early Elsterian ice advance into the southeastern North Sea Basin. The glaciotectonic complex underwent further shortening and the Elsterian tunnel-valley fills that were incised into the glaciotectonic complex were partly deformed during the Saalian Drenthe and Warthe (1) ice advances

Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology - a subgroup analysis of a multicenter, phase III trial

Background: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail. Methods: Whole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 μg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure. Results: A total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916–4608). With a PTV of 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046). Conclusions: Se supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml)

Vergleich differenzierter Darstellung von Funktionen und Bodenschutzanforderungen an ausgewählten Böden des Jahres

Die Erfahrung aus der zehnjährigen Aktion Boden des Jahres zeigt, dass neben Grundkenntnissen der Entwicklung verschiedener Böden, der Beschreibung ihres unterschiedlichen Aufbaus anhand erkennbarer und charakteristischer Merkmale, ihrer Verbreitung, ihrer Nutzung und ihrer Gefährdung zur Herausbildung von nationalem und internationalem Interesse geführt hat. Um den Beitrag zur Herausbildung von Verantwortungsbewusstsein für die knappe Ressource Boden und ihre gegenwärtige Vernutzung in der Gesellschaft zu verstärken, müssen zukünftig die vielfältigen und meist vernetzten Funktionen noch stärker herausgearbeitet und dargestellt werden, auf deren Erhaltung die Menschen, Pflanzen und Tiere angewiesen sind

Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment

PurposeMedication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis. The aim of the present study was to compare the macrophage populations between the craniofacial and extracranial skeleton and to investigate the changes induced by zoledronate (Zol) application and surgical interventions.Materials and methodsAn in vivo experiment was performed. 120 wistar rats were randomized to 4 groups (G1, G2, G3, G4). G1 served as an untreated control group. G2 and G4 received Zol injections for 8 weeks. Afterwards, the right lower molar of the animals from G3 and G4 was extracted and the right tibia osteotomized followed by osteosynthesis. Tissue samples were taken from the extraction socket and the tibia fracture at fixed time points. Immunohistochemistry was conducted to determine the labeling indexes of CD68+ and CD163+ macrophages.ResultsComparing the mandible and the tibia, we observed a significantly higher number of macrophages and a heightened pro-inflammatory environment in the mandible compared to the tibia. Tooth extraction caused an increase of the overall number of macrophages and a shift toward a more pro-inflammatory microenvironment in the mandible. Zol application amplified this effect.ConclusionOur results indicate fundamental immunological differences between the jaw bone and the tibia, which might be a reason for the unique predisposition for MRONJ in the jaw bones. The more pro-inflammatory environment after Zol application and tooth extraction might contribute to the pathogenesis of MRONJ. Targeting macrophages might represent an attractive strategy to prevent MRONJ and improve therapy. In addition, our results support the hypothesis of an anti-tumoral and anti-metastatic effect induced by BPs. However, further studies are needed to delineate the mechanisms and specify the contributions of the various macrophage phenotypes

A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch-German cross-border region, 2017 to 2018:the importance of healthcare structures

BACKGROUND: Antimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders. AIM: The aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows. METHODS: Between September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories. RESULTS: A total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs). CONCLUSIONS: This first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures

Immune function biomarkers in children exposed to lead and organochlorine compounds: a cross-sectional study

BACKGROUND: Different organochlorines and lead (Pb) have been shown to have immunomodulating properties. Children are at greater risk for exposure to these environmental toxicants, but very little data exist on simultaneous exposures to these substances. METHODS: We investigated whether the organochlorine compounds (OC) dichlorodiphenylethylene (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (γ-HCH), the sum of polychlorinated biphenyls (ΣPCBs) and Pb were associated with immune markers such as immunoglobulin (Ig) levels, white blood cell (WBC), counts of lymphocytes; eosinophils and their eosinophilic granula as well as IgE count on basophils. The investigation was part of a cross-sectional environmental study in Hesse, Germany. In 1995, exposure to OC and Pb were determined, questionnaire data collected and immune markers quantified in 331 children. For the analyses, exposure (OC and Pb) concentrations were grouped in quartiles (γ-HCH into tertiles). Using linear regression, controlling for age, gender, passive smoking, serum lipids, and infections in the previous 12 months, we assessed the association between exposures and immune markers. Adjusted geometric means are provided for the different exposure levels. RESULTS: Geometric means were: DDE 0.32 μg/L, ΣPCBs 0.50 μg/L, HCB 0.22 μg/L, γ-HCH 0.02 μg/L and Pb 26.8 μg/L. The ΣPCBs was significantly associated with increased IgM levels, whereas HCB was inversely related to IgM. There was a higher number of NK cells (CD56+) with increased γ-HCH concentrations. At higher lead concentrations we saw increased IgE levels. DDE showed the most associations with significant increases in WBC count, in IgE count on basophils, IgE, IgG, and IgA levels. DDE was also found to significantly decrease eosinophilic granula content. CONCLUSION: Low-level exposures to OC and lead (Pb) in children may have immunomodulating effects. The increased IgE levels, IgE count on basophils, and the reduction of eosinophilic granula at higher DDE concentrations showed a most consistent pattern, which could be of clinical importance in the etiology of allergic diseases

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029